Hormonal methods of fertility control in men that depend on the sustained suppression of gonadotropin secretion require the concomitant administration of an androgen to maintain androgenic functions, including libido. The Population Council has pioneered the development of the synthetic androgen, 7a-methyl-19- nortestosterone (MENT[unreadable]) for male contraception. The evidence suggests that MENT acts much like other androgens to suppress gonadotropin secretion, thereby lowering testicular T levels below the point needed to sustain spermatogenesis. It is much more potent than T in suppressing gonadotropins, thus making it feasible for long-term delivery via sustained release formulations such as silastic implants. MENT is resistant to 5a-reduction, with the potential advantage of being safer for the prostate when used as a contraceptive. In addition, through its conversion to estrogen, MENT should be able to maintain a positive effect on bone mass. Hence, the long-term use of MENT in men is expected to have health benefits in addition to its contraceptive effect. Efficacy of MENT Ac implants to induce azoospermia has been demonstrated in previous studies, and further research is warranted to confirm the safety and efficacy of MENT use for male contraception. In the current proposal we will investigate the safety and efficacy of MENT in animal models as well as in clinical trials. 1) The pharmacological effects of MENT on kidney enzymes and 2) bone growth will be investigated in animal models. 3) A reversibility of fertility study in male rats treated with MENT and a long-acting progestin will be conducted by mating tests with female rats. 4) The effect of MENT will be compared to T in a clinical safety study assessing androgen action on vascular parameters. 5) We will develop and formulate an improved subdermal implant delivery system for the sustained release of MENT (rather than MENT Ac used in previous studies). MENT is preferred over MENT Ac as it is the active component in vivo. 6) A contraceptive efficacy study will be conducted using MENT implants and a longacting progestin.